The primary objective of the proposed work is to investigate the following hypothesis: Risk factors for stroke create a state in which the probability of an interaction between monocyte/macrophages and endothelial cells which could lead to local thrombosis or hemorrhage in focal regions of the brain vasculature is increased. The general design of the work will compare the activity and functional state of stimulated mononuclear cells and endothelial cells from animals with and without risk factors for stroke and to gauge the interaction between these cells. The analyses will proceed from the whole animal to whole brain to isolated microcirculatory brain vessels to isolated microglia ("brain macrophages") and isolated brain microcirculatory endothelial cells. Ultrastructural studies and measurement of such cellular products as IL-1, TNF, eicosanoids, and platelet activating factor (PAF), as well as fibrinopeptide A (FPA), B, 15-42 related peptides (110 RPs), CDw 18 receptors on leukocytes and development of procoagulant activity by endothelium in vitro in response to a provocative stimulus, endotoxin (lipopolysaccharide-LPS), should permit direct testing of the above hypothesis.